Autologous CAR-T/TCR-T Cell Immunotherapy for Solid Malignancies

Inclusion Criteria

• •1. Patients must be willing to sign an informed consent.
• •2. Male or female patients aged 18 to 70 years .
• •3. Estimated survival of ≥ 12 weeks.
• •4. Pathological sections with positive expression of NY-ESO-1, Mesothelin, EGFRvIII and DR5 was confirmed by biopsy IHC test within 12 months.If NY-ESO-1 is positive expression ,positive HLAA\*0201 is required at the same time.
• •5. Solid tumor must have at least one measureable disease according to RECIST 1.1.
• •6. Routine blood test#hemoglobin\>=90 g/L; platelet\>=50×10\^9/L.
• •7. Liver function:ALT and AST≤2.5 times upper limits of normal (If the tumor infiltration is the main cause of abnormal liver function ,ALT and AST≤5 times upper limits of normal); bilirubin\<2.0 mg/dL.
• •8. Renal function:BUN: 9-20mg / dl; serum creatinine≤ 1.5 times upper limits of normal; endogenous creatinine clearance rate≥50 ml/min .
• •9. Negative serum antibody for EBV, CMV, HIV , syphilis, HBVa nd HCV.
• •10. Cardiac function: stable hemodynamic and left ventricular ejection fraction (LVEF)\>=55%.
• •11. ECOG score:0-1.
• •12. Adequate venous access for apheresis, and no other contraindications for leukapheresis .
• •13. Women of child-bearing age must have evidence of negative pregnancy test. Subjects of reproductive potential must agree to use acceptable birth control methods within 1 year after treatment, as described in protocol.
• •14. Subjects with hypertension/diabetes must be stable blood pressure/blood glucose or ≤CTCAE 1 level 2 weeks before the screening.
• •In addition to the above criteria for inclusion, the following criteria shall be met according to the indications:
• •Patients with glioblastoma：
• •1. First disease progression or disease recurrence (≥ 1 cm and ≤ 5 cm) of a supratentorial WHO grade IV malignant glioma (GBM or gliosarcoma) based on imaging studies with measurable disease.
• •2. EGFRvIII, the target antigen, must be identified on tumor tissue by IHC or PCR, i.e. EGFRvIII positive via pathology report.
• •3. Insensitivity to chemoradiotherapy or chemoradiotherapy failure after operation molecular pathology.
• •4. Refused to receive radiotherapy or chemotherapy treatment.
• •Patients with liver cancer
• •1. DR5 or EGFRvIII positive via pathology report.
• •2. Untreatable by surgery ; Or postoperative recurrence ;Or no effective treatment.
• •3. Liver function：child-pugh A grade or child-pugh B grade.
• •Patients with gastric cancer
• •1. Mesothelin positive via pathology report.
• •2. The pathological stage：IIIA～IV.
• •3. chemoradiotherapy failure
• •4. Refused or unable to get surgery.
• •Patients with esophageal cancer
• •1. NY-ESO-1 positive via pathology report and HLA-A\*0201 positive in blood.
• •2. Refuse or unable to get surgery.
• •3. Postoperative recurrence or chemoradiotherapy failure.